Treatment of agitation in delirious hospital patients receiving end-of-life care may be improved by use of a benzodiazepine alongside an antipsychotic agent

medwireNews: The addition of lorazepam to haloperidol significantly reduces agitation associated with delirium in advanced cancer patients receiving palliative care in a hospital setting, suggests research published in JAMA.

“The study findings support the therapeutic role of lorazepam when given in combination with haloperidol as a single-dose rescue to patients with refractory agitation despite scheduled haloperidol”, say David Hui, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

The primary outcome of the single centre study was a change in the Richmond Agitation–Sedation Scale (RASS) score 8 hours after intravenous administration of the benzodiazepine lorazepam 3 mg or placebo after earlier intravenous dosing of haloperidol 2 mg at onset of agitation. The 10-point RASS scale ranges from –5 points for patients who cannot be aroused to 0 points for patients who are alert and calm, and 4 points for patients who are combative.

Of the 90 patients who were randomly assigned to receive treatment, 58 received a study treatment and 52 completed the trial. Before treatment, patients in both arms had a mean RASS score of 1.6. Lorazepam plus haloperidol achieved a 4.1 point reduction in RASS score compared with a 2.3 point reduction with placebo plus haloperidol, resulting in a significant 1.9 point difference in score reduction between the arms.

Patients given lorazepam plus haloperidol also required significantly less use of rescue neuroleptics than controls (median 2.0 vs 4.0 mg) and were significantly more likely to be perceived as being comfortable, as reported by both blinded caregivers (84 vs 37%) and nurses (77 vs 30%).

By contrast, the secondary endpoints of delirium recall and related distress, capacity to communicate and respiratory rate did not significantly differ between the treatment groups, and survival was also similar, David Hui et al say.

Safety analysis revealed hypokinesia to be the most common side effect in both treatment groups, affecting 19% of patients given lorazepam plus haloperidol and 27% of controls, followed by akathisia in 19% and 7%, respectively.

Acknowledging that many patients who might prefer to die at home require hospital care for delirium with agitation, the authors remark: “Both lorazepam and haloperidol are available as oral medications including a rapid sublingual form of lorazepam.

“Further research is needed to examine if these treatment options are feasible and effective for patients with agitated delirium in the home setting.”

The authors of a linked editorial caution, however, that the study findings only “pertain to patients in palliative care units near the end of life who are experiencing hyperactive delirium, and the findings should not be considered generalizable to the patients in, for example, the intensive care unit”.

“This is important given that benzodiazepines, as a class of medications, have been shown to be independently associated with delirium in a wide range of populations”, write Pratik Pandharipande and E Wesley Ely, from the Vanderbilt University School of Medicine in Nashville, Tennessee, USA.

The editorialists emphasize that use of psychoactive medication for persistent hyperactive delirium should be considered in the context of the patient’s physical, medical, psychological and spiritual needs, support for their family members, and respect for the views of care team members.

“The decision to use such powerful medications should be individualized for the patient using the lowest-possible doses of targeted antipsychotic medications or benzodiazepines rather than a one-size-fits-all protocol”, they conclude.